Are we proof that a drug to stop diseases like diabetes DOES work?
Are we proof that a revolutionary new drug to stop diseases like arthritis and type 1 diabetes really DOES work?
The tell-tale sign that 11-year-old Mahn Singh had type 1 diabetes was all too obvious for his father Harj. ‘I suspected he had it because he was suddenly getting up to pee in the night, which is one of the symptoms,’ says Harj, 49, a financial adviser from Ealing, West London, who was himself diagnosed with the condition aged 14.
‘I had the blood testing kit because I use it every day, so I gave him the fingerprick test — and sure enough it was 21.9, which is very high.
‘It was a terrible shock, we didn’t want to believe it. My wife Sharon and I lay awake talking about what to do.
‘It was about midnight; so the next morning we took him to the hospital. They did their tests and confirmed he had type 1 diabetes.
‘It was May 2020 — the height of the Covid lockdown. The doctors wanted to keep him in hospital alone, but I managed to convince them that as a diabetic myself, I knew enough to manage his condition at home, but it was not a good time.’
The tell-tale sign that 11-year-old Mahn Singh (pictured) had type 1 diabetes was all too obvious for his father Harj
Mahn has become the first British child to be part of a trial for a revolutionary new drug, teplizumab. File image
Type 1 diabetes is a form of autoimmune disease, where the body attacks itself; in this case, an immune system malfunction leads it to destroy the cells in the pancreas that produce the hormone insulin, which regulates blood sugar levels.
High circulating blood sugar can cause long-term damage to veins and arteries, the heart, kidneys, eyes and nerves.
Meanwhile, low blood sugar can be equally risky and, left untreated, can cause dizziness, fainting, muscle weakness — and in extreme cases can lead to seizures, unconsciousness and (although more rarely) death, as the brain is starved of fuel and shuts down.
Most patients with type 1 need insulin injections regularly throughout the day — for life — to keep blood sugar levels stable.
The timing and dosage has to be carefully calibrated by the patients themselves, which can be a massive burden on the 400,000 people currently living with it.
Now all that may be about to change.
Mahn has become the first British child to be part of a trial for a revolutionary new drug, teplizumab, which blocks the immune system malfunction that destroys insulin-producing cells and causes type 1 diabetes. The idea is that such drugs will halt the autoimmune disease in its tracks, preventing life-changing symptoms — and the burden on healthcare systems.
Years after first trial I’m still symptom-free
Mikayla Olsen was recruited to the original, groundbreaking teplizumab trial in the U.S. (see main piece), in April 2016, when she was 14.
Her younger sister Mia had been previously diagnosed with type 1 diabetes and after she collapsed, aged nine, from hypoglycaemia [low blood sugar], the whole family was tested for the antibodies known to cause the disease.
‘Mia just stopped responding when my mother talked to her,’ recalls Mikayla, now 21 and a university student.
‘She had to be evacuated in a hospital helicopter and was there for four days while they stabilised her. We almost lost her; her kidneys had stopped working and she had fluid in her lungs.
‘The whole family was tested to see if we also had type 1 diabetes antibodies. I had four out of the five antibodies — meaning I’d probably develop diabetes symptoms pretty soon — everyone else was clear.’ She was subsequently enrolled into a trial comparing teplizumab infusions with dummy treatment.
Mikayla still doesn’t know which she got, but six-and-a-half years later she still has no symptoms of diabetes and does not need insulin.
‘I feel pretty good,’ she says. ‘It’s just sad Mia couldn’t get it.’
Doctors have hailed teplizumab as a game-changer — not least because promising results so far have raised hopes of similar treatments to stop all autoimmune conditions, which affect four million people in the UK.
These include rheumatoid arthritis (where the immune system mistakenly attacks the joints); psoriasis (which affects skin); coeliac disease (which affects the gut); multiple sclerosis (where it attacks the nerve fibres); and lupus (where instead of fighting off infection, the body’s defences malfunction and produce molecules that attack immune cells).
What’s more, in parallel with this treatment advance is one in diagnostics: Britain could become the first country in the world to screen all children in early life for type 1 diabetes antibodies — the cells primed to destroy insulin-producing cells. This follows the discovery of five antibodies unique to the condition. The idea is that if they test positive for the antibodies, they could then be given teplizumab, or similar drugs, early enough to prevent type 1 developing, in a programme that could save thousands from a lifetime of insulin dependency and complications from the condition (which include heart disease and a greater risk of premature death).
‘Controlling very high or very low blood sugar is a nightmare,’ says Harj. ‘My wife has had to deal with my low sugar hypos where I’m confused, dizzy, sick; it’s not nice. It can go up or down without warning — due to the weather, altitude, stress — and it’s life-threatening. I had to go into hospital twice when I was a teenager and was warned if I didn’t do what I was told I would die,’ he says. ‘But trying to live with diabetes had really got to me. I refused to inject myself with insulin. I didn’t want Mahn to have the life I’ve had and I was determined to do more for him. When I found out about the teplizumab trial, I had to make sure he was in it.’
Thanks to his father’s determination, Mahn, now 14, was the first patient in the UK to be enrolled in the study, receiving his first infusion of it in June 2020. ‘I discovered one of the trial centres was Sheffield so we had to go up there for it,’ Harj says. ‘Mahn tested positive for three of the five type 1 diabetes autoantibodies.’
The study Mahn is participating in, called Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab (PROTECT) involves 330 eight to 18-year-olds worldwide, nine of them in the UK.
The UK participants are being treated at Northwick Park Hospital in London, University Hospital of Wales in Cardiff and Sheffield Children’s NHS Foundation Trust. All are having two 14-day infusions, in hospital, six months apart.
Like other advanced trials, half of the participants receive a dummy treatment and half the active drug in the ‘double-blind’ study, where neither doctors nor patients know who gets what.
‘We won’t know until the summer when the trial ends, but I think Mahn had the drug, not the dummy infusion,’ says Harj.
‘He is on some insulin but I think it’s helped to keep working whatever functioning insulin-producing cells he had.’ Teplizumab, which blocks the action of insulin cell-destroying antibodies in type 1, could pave the way for ‘insulin-free type 1 diabetes’, says Professor Colin Dayan, chair of clinical diabetes and metabolism at Cardiff University, who is leading the UK arm of the PROTECT trial.
‘Our ultimate ambition is insulin-free type 1 diabetes and this is the first step towards it,’ he says.
Teplizumab was first used in a U.S. trial of 76 type 1 patients — most of them teenagers — which had spectacular results: less than half of those who received teplizumab have gone on to develop type 1, compared to 72 per cent of those who received a placebo, reported the New England Journal of Medicine. These patients are still being monitored and among those who received the active drug, many have lived for more than a decade without developing type 1 diabetes, meaning the drug had blocked the destruction of their insulin-producing cells and their natural healthy pancreas function had been protected.
Last November, the U.S. medicines regulator, the Food and Drug Administration, approved the use of teplizumab for children aged eight or above.
The drug has not been tested on those who’ve had type 1 for years, because it cannot restore the insulin-producing cells once they have been destroyed — which is why it must be given as early as possible.
Dr Kevan Herold, a senior diabetes specialist at Yale School of Medicine, who led the original U.S. trial, says the results have been dramatic.
Some of the people given this drug have gone a decade or more without developing diabetes,’ he told Good Health. ‘One of the strengths of teplizumab is it doesn’t involve long-term immunosuppression [which is the usual type of treatment for stopping autoimmune type damage]. It is given for a short period with lasting effects and, therefore, the risk is minimised.’
For reasons that are unclear, Britain has one of the world’s highest rates of type 1 diabetes. Around 400,000 people are affected and the number of new diagnoses is rising by up to 5 per cent per year.
The other form, type 2 diabetes, affects almost five million Britons and is most commonly associated with obesity, as the body struggles with metabolic overload.
While about 15 per cent of new cases of type 1 occur in children such as Mahn with an affected parent, the vast majority occur spontaneously and without warning.
For many the first signs include worsening attacks of confusion or shaking, caused by very low blood sugar — which may be too late to reverse, as many of the insulin-producing cells in the pancreas would have already been destroyed. Advances in diagnosis, thanks to the discovery of the five unique antibodies in blood that cause the condition — followed by a treatment regimen using teplizumab — are together offering the real prospect of thousands of children avoiding the lifelong difficulties associated with insulin dependency.
Indeed, the international Juvenile Diabetes Research Foundation has calculated that a person with type 1 diabetes will have around 65,000 injections and measure their blood sugar more than 80,000 times in their lifetime.
The condition can also lead to depression as patients may struggle to control their lifestyle and blood sugar. There is also a potential long-term health burden.
The NHS National Diabetes Audit report has shown that people between the ages of 35 and 64 living with type 1 diabetes are three to four times more likely to die prematurely than those without the condition.
‘There’s huge value in identifying who is at risk from type 1 diabetes using antibody testing,’ explains Dr Herold. ‘The majority of people who get it don’t have relatives with the disease. I think of this as an opening opportunity for immune diseases, similar to the huge advances in cancer treatment.’
Professor Dayan adds: ‘I would hope Britain will be the first country to introduce screening and we have already begun conversations with the National Screening Committee. An early blood fingerprint done at the age of three at the same time as pre-school vaccines such as MMR would pick up 50 to 70 per cent of the children who are going to get type 1 diabetes.
‘This is disruptive technology — I hope the results of these trials will start people thinking in a different way.’
Dr Rachel Besser is a consultant paediatrician who specialises in type 1 diabetes and lead of the T1Early programme on general population screening for type 1 diabetes at Oxford University. She has lived with it herself since the age of nine. She says: ‘You never get a day off with diabetes, it can be very difficult to control and can be harder for parents than children because they are constantly worrying about it.
‘Before we can even think about national screening we need to know the best way to do it, so the benefits outweigh any potential harms — but teplizumab is undoubtedly a game-changer and one which I never thought would happen in my lifetime.’
Doctors are optimistic that other groundbreaking drugs will now change the landscape for patients with type 1 and other autoimmune conditions.
Ustekinumab, which is similar to teplizumab, is being tested in patients aged 12 to 18 who’ve been diagnosed with type 1 diabetes within the previous 100 days.
The aim is to see if it also blocks the destruction of insulin-producing cells.
It is already licensed for psoriasis and inflammatory bowel disease (both autoimmune conditions), and has had some success in reducing symptoms of type 1 and disease progression.
Daisy Abbs, 14, from Harrogate, North Yorkshire, has been in a trial of ustekinumab (but her family don’t yet know if she received the active drug or a placebo).
She was diagnosed with type 1 in July 2020, just a few days after her 12th birthday.
‘She had suddenly got a lot thinner for no reason and seemed to have no energy,’ says her mother Kathy, 50, an NHS administrator. ‘The doctor wanted a urine sample which I had dropped off at the practice. I got back to the house less than half an hour later and they called, telling us to go straight to hospital. When we got there, I was told it was lucky they caught Daisy in time because she was close to a coma she might not have woken up from.
‘Of all the life-threatening diseases you think you have to protect your child from, this has never been one of them,’ says Kathy, who lives with husband Jason, 51, who designs show jumping courses, Daisy, and daughter Poppy, 17.
She acknowledges the difficulties of regulating her teen daughter’s insulin needs: ‘The difference between a fatal insulin dose and what’s going to keep them alive is tiny,’ she says.
Meanwhile, such is the level of excitement around teplizumab that the Medicines and Healthcare products Regulatory Agency (MHRA) has awarded it an ‘Innovation Passport’ for a speeded-up approval process, designed to give faster access to promising new medicines.
An MHRA spokesman said last week that ‘due to commercial confidentiality, we are not able to comment on timeframes for potential approvals’.
However, when it comes to introducing screening, the Department of Health and Social Care confirmed last week that there are already ‘ongoing discussions with the Antenatal and Newborn Research and Innovation Advisory Committee around this topic’.
Hilary Nathan, director of Communications and Policy at the Juvenile Diabetes Research Foundation, told Good Health: ‘Population screening to detect type 1 in its earliest stage is crucial to help prevent people becoming seriously ill before their condition is diagnosed.
‘In the UK today, a quarter of children are diagnosed with type 1 in a life-threatening emergency, because their initial symptoms were missed.
‘By identifying people who are at risk, we can prevent this heartbreaking outcome.
‘We also hope that we’ll soon have access to disease-modifying drugs such as teplizumab. When disease-modifying treatments are licensed in the UK, we’ll need screening to identify people in the earliest stage, who would benefit.’
Which other conditions might it help?
The extraordinary results from teplizumab trials for type 1 diabetes have attracted growing interest from doctors treating other autoimmune diseases — though this is tempered according to the nature of the condition they treat.
Rheumatoid arthritis affects at least 430,000 people in the UK and once joints are damaged nothing can restore their condition.
‘There are genetic markers for rheumatoid arthritis and people with them are prone to more severe forms of the disease,’ says Dr Wendy Holden, a consultant rheumatologist and adviser to the charity Arthritis UK.
‘Teplizumab is a game-changer and the targeting of these kind of markers could be very relevant to our patients, too.’
It was initially announced as a treatment for lupus — an over-production of antibodies that can cause painful inflammation around the body. But Paul Howard, spokesman for the charity Lupus UK, cautions: ‘[The manufacturer] overstates the potential impact these drugs can have for disease management. Trial results have not been that great. There are lots of “biologic” therapies that target specific elements of the immune system being used to treat autoimmune diseases, but none of them have a curative effect.’
Multiple sclerosis affects 130,000 in the UK and is caused by the immune system attacking nerve fibres. ‘We have some of these so-called disease-modifying therapies already where drugs slow down the processes, but there’s a massive unmet need for better treatment,’ said MS Society spokesman Joe Brunwin.
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